Departments of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
Am J Surg Pathol. 2019 Jun;43(6):773-782. doi: 10.1097/PAS.0000000000001243.
BCOR immunoreactivity is a sensitive and highly specific marker for clear cell sarcoma of the kidney (CCSK). However, a subset of adult renal sarcomas which overexpress BCOR are negative for BCOR genetic alterations, including BCOR gene fusions or BCOR-internal tandem duplication, and thus remain unclassified. We report 5 such undifferentiated renal/perirenal sarcomas which raised the differential diagnosis of CCSK due to their morphologic appearance and strong BCOR immunoreactivity, but which on RNA sequencing proved to be malignant solitary fibrous tumors (SFTs). The neoplasms occurred in patients at an age range of 30 to 62 years. Three patients were females and 2 male. Four were primary renal neoplasms while one was perirenal. All 5 neoplasms were cellular, nonpleomorphic, undifferentiated sarcomas with branching capillary vasculature composed of primitive round to ovoid neoplastic cells with scant cytoplasm and nuclei having fine, evenly dispersed chromatin. None of the cases demonstrated the typical hyperchromatic fusiform nuclei, prominent collagen deposition, or hemangiopericytomatous vasculature of SFT. All 5 cases were strongly immunoreactive for BCOR. Three cases were CD34 negative, where the other 2 were only focally CD34 positive. STAT6 was subsequently found to be positive by immunohistochemistry in all 5 cases. In summary, we report a previously unrecognized mimic of CCSK: malignant SFTs with an undifferentiated/small round cell phenotype along with branching capillary vasculature, strong immunoreactivity for BCOR, and minimal or no immunoreactivity for CD34. As CCSK is treated with a specific chemotherapy regimen, this distinction has therapeutic implications.
BCOR 免疫反应是肾透明细胞肉瘤 (CCSK) 的敏感且高度特异的标志物。然而,一组过度表达 BCOR 的成人肾肉瘤对 BCOR 基因改变呈阴性,包括 BCOR 基因融合或 BCOR 内部串联重复,因此仍未分类。我们报告了 5 例这样的未分化的肾/肾周肉瘤,由于其形态学表现和强烈的 BCOR 免疫反应,提高了 CCSK 的鉴别诊断,但通过 RNA 测序证明它们是恶性孤立性纤维瘤 (SFT)。这些肿瘤发生在年龄 30 至 62 岁的患者中。3 名患者为女性,2 名男性。4 例为原发性肾肿瘤,1 例为肾周肿瘤。所有 5 例肿瘤均为细胞性、非多形性、未分化肉瘤,分支毛细血管血管由原始圆形至卵圆形的肿瘤细胞组成,细胞质稀少,细胞核具有精细、均匀分散的染色质。没有一例表现出典型的高度嗜色性梭形核、显著的胶原沉积或 SFT 的血管外皮细胞瘤样血管。所有 5 例均强烈表达 BCOR。3 例 CD34 阴性,另外 2 例仅局灶性 CD34 阳性。免疫组化随后发现所有 5 例均为 STAT6 阳性。总之,我们报告了一种以前未被认识到的 CCSK 模拟物:恶性 SFT 具有未分化/小圆细胞表型,伴有分支毛细血管血管,强烈的 BCOR 免疫反应,以及最小或无 CD34 免疫反应。由于 CCSK 采用特定的化疗方案治疗,因此这种区别具有治疗意义。